title: LKB1 downregulation may be independent of promoter methylation or FOXO3 expression in head and neck cancer.
abstract: The serine/threonine kinase liver kinase B 1 (LKB1) is a multifunctional protein and has been associated with various cancer types. Although the tumor suppressor function of LKB1 is attributed mainly to its ability to phosphorylate directly different adenosine monophosphate-activated protein kinases, its regulation is still poorly understood. More recently, it has been shown that LKB1 expression can be regulated by forkhead box O transcription factors via cis-acting elements, which are found in the promoter region of the LKB1 gene. In this study, we investigated LKB1 messenger RNA expression levels in association with the promoter methylation of the gene and forkhead box O member 3 (FOXO3) messenger RNA expression in head and neck squamous cell carcinoma (HNSCC) tumor samples. Our results show that LKB1 expression is downregulated, especially in advanced-stage tumor samples, and this downregulation was not the result of promoter methylation or modulation by FOXO3 (P = 0.656). Despite observing a positive association between the LKB1 and FOXO3 expression levels in the tumors, this association was not statistically significant (P = 0.24). Our results indicate that downregulation of LKB1 is independent of FOXO3 and may be implicated in the progression of HNSCC.
authors.affiliation: Cerrahpasa Medical Faculty, Department of Medical Biology, Istanbul University, Turkey.
authors.forename: Seda
authors.initials: S
authors.lastname: Ekizoglu
authors.forename: Nejat
authors.initials: N
authors.lastname: Dalay
authors.forename: Emin
authors.initials: E
authors.lastname: Karaman
authors.forename: Demet
authors.initials: D
authors.lastname: Akdeniz
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozaydin
authors.forename: Nur
authors.initials: N
authors.lastname: Buyru
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019175:DNA Methylation; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D020868:Gene Silencing; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases
keywords: FOXO; FOXO3; HNC; HNSCC; HPV; LKB1; PCR; PJS; Peutz-Jeghers syndrome; forkhead box O; forkhead box O member 3; head and neck carcinoma; head and neck squamous cell carcinoma; human papillomavirus; liver kinase B1; mRNA; messenger RNA; polymerase chain reaction